Cargando…

Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Rep...

Descripción completa

Detalles Bibliográficos
Autores principales: Pazoki, Raha, Vujkovic, Marijana, Elliott, Joshua, Evangelou, Evangelos, Gill, Dipender, Ghanbari, Mohsen, van der Most, Peter J., Pinto, Rui Climaco, Wielscher, Matthias, Farlik, Matthias, Zuber, Verena, de Knegt, Robert J., Snieder, Harold, Uitterlinden, André G., Lynch, Julie A., Jiang, Xiyun, Said, Saredo, Kaplan, David E., Lee, Kyung Min, Serper, Marina, Carr, Rotonya M., Tsao, Philip S., Atkinson, Stephen R., Dehghan, Abbas, Tzoulaki, Ioanna, Ikram, M. Arfan, Herzig, Karl-Heinz, Järvelin, Marjo-Riitta, Alizadeh, Behrooz Z., O’Donnell, Christopher J., Saleheen, Danish, Voight, Benjamin F., Chang, Kyong-Mi, Thursz, Mark R., Elliott, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110798/
https://www.ncbi.nlm.nih.gov/pubmed/33972514
http://dx.doi.org/10.1038/s41467-021-22338-2
_version_ 1783690364274606080
author Pazoki, Raha
Vujkovic, Marijana
Elliott, Joshua
Evangelou, Evangelos
Gill, Dipender
Ghanbari, Mohsen
van der Most, Peter J.
Pinto, Rui Climaco
Wielscher, Matthias
Farlik, Matthias
Zuber, Verena
de Knegt, Robert J.
Snieder, Harold
Uitterlinden, André G.
Lynch, Julie A.
Jiang, Xiyun
Said, Saredo
Kaplan, David E.
Lee, Kyung Min
Serper, Marina
Carr, Rotonya M.
Tsao, Philip S.
Atkinson, Stephen R.
Dehghan, Abbas
Tzoulaki, Ioanna
Ikram, M. Arfan
Herzig, Karl-Heinz
Järvelin, Marjo-Riitta
Alizadeh, Behrooz Z.
O’Donnell, Christopher J.
Saleheen, Danish
Voight, Benjamin F.
Chang, Kyong-Mi
Thursz, Mark R.
Elliott, Paul
author_facet Pazoki, Raha
Vujkovic, Marijana
Elliott, Joshua
Evangelou, Evangelos
Gill, Dipender
Ghanbari, Mohsen
van der Most, Peter J.
Pinto, Rui Climaco
Wielscher, Matthias
Farlik, Matthias
Zuber, Verena
de Knegt, Robert J.
Snieder, Harold
Uitterlinden, André G.
Lynch, Julie A.
Jiang, Xiyun
Said, Saredo
Kaplan, David E.
Lee, Kyung Min
Serper, Marina
Carr, Rotonya M.
Tsao, Philip S.
Atkinson, Stephen R.
Dehghan, Abbas
Tzoulaki, Ioanna
Ikram, M. Arfan
Herzig, Karl-Heinz
Järvelin, Marjo-Riitta
Alizadeh, Behrooz Z.
O’Donnell, Christopher J.
Saleheen, Danish
Voight, Benjamin F.
Chang, Kyong-Mi
Thursz, Mark R.
Elliott, Paul
author_sort Pazoki, Raha
collection PubMed
description Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.
format Online
Article
Text
id pubmed-8110798
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-81107982021-05-14 Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes Pazoki, Raha Vujkovic, Marijana Elliott, Joshua Evangelou, Evangelos Gill, Dipender Ghanbari, Mohsen van der Most, Peter J. Pinto, Rui Climaco Wielscher, Matthias Farlik, Matthias Zuber, Verena de Knegt, Robert J. Snieder, Harold Uitterlinden, André G. Lynch, Julie A. Jiang, Xiyun Said, Saredo Kaplan, David E. Lee, Kyung Min Serper, Marina Carr, Rotonya M. Tsao, Philip S. Atkinson, Stephen R. Dehghan, Abbas Tzoulaki, Ioanna Ikram, M. Arfan Herzig, Karl-Heinz Järvelin, Marjo-Riitta Alizadeh, Behrooz Z. O’Donnell, Christopher J. Saleheen, Danish Voight, Benjamin F. Chang, Kyong-Mi Thursz, Mark R. Elliott, Paul Nat Commun Article Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease. Nature Publishing Group UK 2021-05-10 /pmc/articles/PMC8110798/ /pubmed/33972514 http://dx.doi.org/10.1038/s41467-021-22338-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Pazoki, Raha
Vujkovic, Marijana
Elliott, Joshua
Evangelou, Evangelos
Gill, Dipender
Ghanbari, Mohsen
van der Most, Peter J.
Pinto, Rui Climaco
Wielscher, Matthias
Farlik, Matthias
Zuber, Verena
de Knegt, Robert J.
Snieder, Harold
Uitterlinden, André G.
Lynch, Julie A.
Jiang, Xiyun
Said, Saredo
Kaplan, David E.
Lee, Kyung Min
Serper, Marina
Carr, Rotonya M.
Tsao, Philip S.
Atkinson, Stephen R.
Dehghan, Abbas
Tzoulaki, Ioanna
Ikram, M. Arfan
Herzig, Karl-Heinz
Järvelin, Marjo-Riitta
Alizadeh, Behrooz Z.
O’Donnell, Christopher J.
Saleheen, Danish
Voight, Benjamin F.
Chang, Kyong-Mi
Thursz, Mark R.
Elliott, Paul
Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
title Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
title_full Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
title_fullStr Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
title_full_unstemmed Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
title_short Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes
title_sort genetic analysis in european ancestry individuals identifies 517 loci associated with liver enzymes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110798/
https://www.ncbi.nlm.nih.gov/pubmed/33972514
http://dx.doi.org/10.1038/s41467-021-22338-2
work_keys_str_mv AT pazokiraha geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT vujkovicmarijana geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT elliottjoshua geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT evangelouevangelos geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT gilldipender geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT ghanbarimohsen geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT vandermostpeterj geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT pintoruiclimaco geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT wielschermatthias geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT farlikmatthias geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT zuberverena geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT deknegtrobertj geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT sniederharold geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT uitterlindenandreg geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT lynchjuliea geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT jiangxiyun geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT saidsaredo geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT kaplandavide geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT leekyungmin geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT serpermarina geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT carrrotonyam geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT tsaophilips geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT atkinsonstephenr geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT dehghanabbas geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT tzoulakiioanna geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT ikrammarfan geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT herzigkarlheinz geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT jarvelinmarjoriitta geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT alizadehbehroozz geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT odonnellchristopherj geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT saleheendanish geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT voightbenjaminf geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT changkyongmi geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT thurszmarkr geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT elliottpaul geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes
AT geneticanalysisineuropeanancestryindividualsidentifies517lociassociatedwithliverenzymes